Evidence-Based Medicine
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2017; 23(25): 4644-4653
Published online Jul 7, 2017. doi: 10.3748/wjg.v23.i25.4644
Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis
Mi-Rae Shin, Hyo-Jin An, Bu-Il Seo, Seong-Soo Roh
Mi-Rae Shin, Hyo-Jin An, Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju-si, Gangwondo 26339, South Korea
Bu-Il Seo, Seong-Soo Roh, Department of Herbology, College of Korean Medicine, Daegu Haany University, Suseong-gu, Deagu 42158, South Korea
Author contributions: Shin MR performed the majority of experiments and wrote the paper; Seo BI analyzed the data; An HJ and Roh SS designed and coordinated the research; all authors read and approved the final version for publication.
Supported by National Research Foundation of South Korea; and Korean Government (MSIP), No. 2017R1A2B2006858.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Daegu Haany University (No. DHU2016-81).
Conflict-of-interest statement: The authors declare no competing financial interests related to this study or its publication.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Seong-Soo Roh, Professor, Director, College of Korean medicine, Daegu Haany University, 136, Shinchendong-ro, Suseong-gu, Deagu 42158, South Korea. ddede@dhu.ac.kr
Telephone: +82-53-7702296 Fax: +82-53-7686340
Received: January 9, 2017
Peer-review started: January 10, 2017
First decision: February 23, 2017
Revised: March 8, 2017
Accepted: April 12, 2017
Article in press: April 12, 2017
Published online: July 7, 2017
Processing time: 179 Days and 1.4 Hours
Abstract
AIM

To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model.

METHODS

A surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting. Changes in esophageal pathology were analyzed by gross and histological examinations.

RESULTS

The CARE exposure modeled rats showed increased levels of the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment completely resolved these CARE-related increases. The CARE rats also showed markers of cytokine stress, including elevated levels of TNF-α and reactive oxygen species as well as of the consequent increase in JNK activation, and subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic effect, as evidenced by altered expression of the apoptosis-related genes for bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly ameliorated the CARE-related esophageal mucosal ulcerations.

CONCLUSION

In the rat model of CARE, BHSST can suppress development of esophageal mucosal ulceration via regulation of reactive oxygen species-dependent apoptosis.

Keywords: Banhasasim-tang; Chronic acid reflux esophagitis; Reactive oxygen species; Esophageal ulcer; Apoptosis

Core tip: Banhasasim-tang (BHSST) has been used widely as an herbal prescription in East Asia for its therapeutic effects on symptoms associated with gastroesophageal reflux disease. In this study, BHSST is shown to play a protective role against chronic acid reflux esophagitis-induced esophageal mucosal ulcer in a rat model, and that this effect involves regulation of reactive oxygen species-dependent apoptosis.